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Right arrow Lung - transplantation

Ann Thorac Surg 2006;82:472-478
© 2006 The Society of Thoracic Surgeons

Original Articles: General Thoracic

Interleukin-6 Regulation of Direct Lung Ischemia Reperfusion Injury

Alexander S. Farivar, MD, Heather E. Merry, MD, Mauricio J. Fica-Delgado, MD, Anton S. McCourtie, MRCS, Brendan C. Mackinnon-Patterson, BS, Michael S. Mulligan, MD*

Division of Thoracic Surgery, University of Washington Medical Center, Seattle, Washington

Accepted for publication March 14, 2006.

* Address correspondence to Dr Mulligan, University of Washington Medical Center, 1959 NE Pacific St, Box 356310, Seattle, WA 98195. (Email: msmmd{at}u.washington.edu).

Presented at the Poster Session of the Forty-second Annual Meeting of The Society of Thoracic Surgeons, Chicago, IL, Jan 30–Feb 1, 2006.

BACKGROUND: Lung ischemia reperfusion injury continues to adversely affect patient and graft survival after transplantation. While the role of interleukin-6 has been studied in ischemia-reperfusion models of intestine, liver, and heart, its participation in lung reperfusion injury has not been characterized.

METHODS: We administered recombinant interleukin-6 to rat lungs through the intratracheal route before inducing left lung ischemia and reperfusion. Multiple in-vivo indicators of left lung injury were studied, as were transactivation patterns for nuclear factor kappa B and signal transduction and activators of transcription-3. Downstream effects on the elaboration of proinflammatory chemokines and cytokines were also studied.

RESULTS: Recombinant interleukin-6 reduced endothelial disruption and neutrophil sequestration in left lung and alveolar spaces, resulting in improved oxygenation after ischemia and 4 hours of reperfusion. This protection was associated with decreased nuclear factor kappa B and signal transduction and activators of transcription-3 nuclear translocation early in reperfusion, and diminished proinflammatory mediator secretion late in reperfusion.

CONCLUSIONS: Further studies focusing on the effects of recombinant interleukin-6 in large animal models are warranted, as this may be a novel strategy to improve outcomes after lung transplantation. Intratracheal administration may focus its efficacy on the lung while reducing effects on other organ systems during organ procurement.




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T. K. Varghese Jr
Invited commentary
Ann. Thorac. Surg., August 1, 2006; 82(2): 478 - 479.
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